Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity

Importance: Neurological manifestations during acute SARS-CoV-2–related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2–related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2–related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P  Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.</p

Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C

IntroductionHospitalized children diagnosed with SARS-CoV-2-related conditions are at risk for new or persistent symptoms and functional impairments. Our objective was to analyze post-hospital symptoms, healthcare utilization, and outcomes of children previously hospitalized and diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C).MethodsProspective, multicenter electronic survey of parents of children &lt;18 years of age surviving hospitalization from 12 U.S. centers between January 2020 and July 2021. The primary outcome was a parent report of child recovery status at the time of the survey (recovered vs. not recovered). Secondary outcomes included new or persistent symptoms, readmissions, and health-related quality of life. Multivariable backward stepwise logistic regression was performed for the association of patient, disease, laboratory, and treatment variables with recovered status.ResultsThe children [n = 79; 30 (38.0%) female] with acute SARS-CoV-2 (75.7%) or MIS-C (24.3%) had a median age of 6.5 years (interquartile range 2.0–13.0) and 51 (64.6%) had a preexisting condition. Fifty children (63.3%) required critical care. One-third [23/79 (29.1%)] were not recovered at follow-up [43 (31, 54) months post-discharge]. Admission C-reactive protein levels were higher in children not recovered vs. recovered [5.7 (1.3, 25.1) vs. 1.3 (0.4, 6.3) mg/dl, p = 0.02]. At follow-up, 67% overall had new or persistent symptoms. The most common symptoms were fatigue (37%), weakness (25%), and headache (24%), all with frequencies higher in children not recovered. Forty percent had at least one return emergency visit and 24% had a hospital readmission. Recovered status was associated with better total HRQOL [87 (77, 95) vs. 77 (51, 83), p = 0.01]. In multivariable analysis, lower admission C-reactive protein [odds ratio 0.90 (95% confidence interval 0.82, 0.99)] and higher admission lymphocyte count [1.001 (1.0002, 1.002)] were associated with recovered status.ConclusionsChildren considered recovered by their parents following hospitalization with SARS-CoV-2-related conditions had less symptom frequency and better HRQOL than those reported as not recovered. Increased inflammation and lower lymphocyte count on hospital admission may help to identify children needing longitudinal, multidisciplinary care.Clinical Trial RegistrationClinicalTrials.gov (NCT04379089)

Long-term survival of a pediatric hematopoietic cell transplant recipient with Fanconi anemia treated with extracorporeal membrane oxygenation: Case report and review of the literature

Background: Pediatric hematopoietic cell transplant (HCT) patients treated with extracorporeal membrane oxygenation (ECMO) have historically experienced poor outcomes. Recent survey data indicates that critical care providers are more open to offering ECMO therapy to pediatric HCT patients. Recent data has also shown improved survival in this patient population. However, data regarding the use of ECMO in nonmalignant conditions is limited. Case report: We present the first successful use of ECMO for a child with Fanconi anemia. A 5-year-old girl with VACTERL sequence, repaired complex congenital heart disease, and multiple complex medical comorbidities developed respiratory failure after a matched unrelated CD34 selected peripheral blood HCT. The patient was treated with steroids and etanercept and received 8 days of ECMO support. She is now 6 years post-HCT and doing well. Conclusion: We highlight this case due to our patient's high medical complexity and positive long-term outcomes after using ECMO

Effect of dietary cellulose supplementation on gut barrier function and apoptosis in a murine model of endotoxemia.

The gut plays a vital role in critical illness, and alterations in the gut structure and function have been reported in endotoxemia and sepsis models. Previously, we have demonstrated a novel link between the diet-induced alteration of the gut microbiome with cellulose and improved outcomes in sepsis. As compared to mice receiving basal fiber (BF) diet, mice that were fed a non-fermentable high fiber (HF) diet demonstrated significant improvement in survival and decreased organ injury in both cecal-ligation and puncture (CLP) and endotoxin sepsis models. To understand if the benefit conferred by HF diet extends to the gut structure and function, we hypothesized that HF diet would be associated with a reduction in sepsis-induced gut epithelial loss and permeability in mice. We demonstrate that the use of dietary cellulose decreased LPS-mediated intestinal hyperpermeability and protected the gut from apoptosis. Furthermore, we noted a significant increase in epithelial cell proliferation, as evidenced by an increase in the percentage of bromodeoxyuridine-positive cells in HF fed mice as compared to BF fed mice. Thus, the use of HF diet is a simple and effective tool that confers benefit in a murine model of sepsis, and understanding the intricate relationship between the epithelial barrier, gut microbiota, and diet will open-up additional therapeutic avenues for the treatment of gut dysfunction in critical illness

Critical Care and Mechanical Ventilation Practices Surrounding Liver Transplantation in Children: A Multicenter Collaborative

We aimed to determine which characteristics and management approaches were associated with postoperative invasive mechanical ventilation (IMV) and with a prolonged course of IMV in children post liver transplant as well as describing the utilization of critical care resources. Retrospective, multicenter, cohort study of children who underwent an isolated liver transplantation between January 2017 and December 2018. Twelve U.S., pediatric, liver transplant centers. Three hundred thirty children post liver transplant admitted to the ICU. None. Six patients died in our cohort. The median length of PICU stay was 4.5 days (interquartile range [IQR], 2.9-8.2 d). Most patients were initially monitored with arterial catheters (96%), central venous pressures (95%), and liver ultrasound (93%). Anticoagulation (80%), blood product administration (52.4%), and vasoactive agents (23.0%) were commonly used therapies in the first 7 days. In multivariable logistic regression analysis, age (adjusted odds ratio [aOR] 0.9 [0.86-0.95]), open fascia (aOR 7.0 [95% CI, 2.6-18.9]), large center size (aOR 4.3 [95% CI 2.2-8.3]), and higher Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (aOR 1.04 [95% CI, 1.01-1.06]) were associated with postoperative IMV. In multivariable logistic regression analysis, postoperative day 0 peak inspiratory pressure (PIP) (aOR 1.2 [95% CI, 1.1-1.3]), large center size (aOR 2.9 [95% CI, 1.6-5.4]), and age (aOR 0.89 [95% CI, 0.85-0.95]) were associated with length of IMV greater than 24 hours. Length of IMV greater than 24 hours was associated with bleeding complications ( p = 0.03), infections ( p = 0.03), graft loss ( p = 0.02), and reoperation ( p = 0.03). Younger age, preoperative hospitalization, large center size, and open fascia are associated with use of IMV, and younger age, large center size, and postoperative day 0 PIP are associated with prolonged IMV on multivariable analysis. Longer IMV is associated with negative outcomes, making it an important clinical marker